Evaluation Of Anti-Anxiety Effect Of Nifedipine Compared To Diazepam In Swiss Albino Mice Using Behavioural Models

Objective: The present study was undertaken to evaluate the acute and chronic anxiolytic effects of nifedipine in comparison to diazepam using in Swiss Albino mice using two behavioral models. Methods: 30 Swiss albino mice were divided into 5 groups with 6 mice in each group. The study was conducted in two phases to evaluate acute and chronic effects. The groups consisted of diazepam (1 mg/kg), 3 doses of nifedipine (2.6 mg/kg, 5.2 mg/kg and 10.4 mg/kg) and vehicle control. The Elevated Plus Maze (EPM) and Light and Dark box were used to evaluate the anti-anxiety effects. The number of entries and time spent in the open arm of the elevated plus-maze and in the light area of light and dark box model were noted and compared among the 5 groups. Observations were analyzed using ANOVA and post hoc Tukey's test. Results: Nifedipine (5.2 mg/kg and 10.4 mg/kg) significantly increased the number of entries and time spent in the open arm compared to vehicle control in the EPM test (p<0.001). Similarly, in the light and dark box test, nifedipine (5.2 mg/kg and 10.4 mg/kg) increased the number of entries and time spent in the light area compared to vehicle control (p<0.05). However, the low dose of nifedipine (2.6 mg/kg) did not exhibit significant findings. Conclusion: Two doses of nifedipine (5.2 mg/kg and 10.4 mg/kg) possess anti-anxiety effects both on acute and chronic administration in both elevated plus maze and light and dark box model.

In vitro anti-metastatic activity of enterolactone, a mammalian lignan derived from flax lignan, and down-regulation of matrix metalloproteinases in MCF-7 and MDA MB 231 cell lines.

Background: Actin cytoskeleton is involved in actin-based cell adhesion, cell motility, and matrix metalloproteinases(MMPs) MMP2, MMP9, MMP11 and MMP14 are responsible for cell invasion in breast cancer metastasis. The dietary intake of lignan from flax seed gets converted to enterolactone (EL) and enterodiol in the human system. Here we show that the enterolactone has a very significant anti-metastatic activity as demonstrated by its ability to inhibit adhesion and invasion and migration in MCF-7 and MDA MB231 cell lines. Materials and Methods: Migration inhibition assay, actin-based cell motility assay along with reverse transcriptase polymerase chain reaction (RT-PCR) for MMP2, MMP9, MMP11 and MMP14 genes were performed in MCF-7 and MDA MB 231 cell lines. Results: Enterolactone seems to inhibit actin-based cell motility as evidenced by confocal imaging and photo documentation of cell migration assay. The results are supported by the observation that the enterolactone in vitro significantly down-regulates the metastasis-related metalloproteinases MMP2, MMP9 and MMP14 gene expressions. No significant alteration in the MMP11 gene expression was found. Conclusions: Therefore we suggest that the anti-metastatic activity of EL is attributed to its ability to inhibit cell adhesion, cell invasion and cell motility. EL affects normal filopodia and lamellipodia structures, polymerization of actin filaments at their leading edges and thereby inhibits actin-based cell adhesion and cell motility. The process involves multiple force-generating mechanisms of actin filaments i.e. protrusion, traction, deadhesion and tail-retraction. By down-regulating the metastasis-related MMP2, MMP9 and MMP14 gene expressions, EL may be responsible for cell invasion step of metastasis.